Changes In DAS28 Scores Research Articles

Interactions between rheumatoid arthritis antibodies are associated with the response to anti-tumor necrosis factor therapy

BackgroundBlocking of the Tumor Necrosis Factor (TNF) activity is a successful therapeutic approach for 50–60% of rheumatoid arthritis (RA) patients. However, there are yet no biomarkers to stratify patients for anti-TNF therapy. Rheumatoid factor (RF) and anti-cyclic-citrullinated antibodies (anti-CCP) have been evaluated as biomarkers of response but the results have shown limited consistency. Anti-carbamylated protein (anti-CarP) and anti-peptidylarginine deiminase type 4 (anti-PAD4) antibodies have been much less studied. Despite being linked to common immune processes, the interaction between these markers has not been evaluated yet. Our aim was to analyze the interaction between these four antibodies in relation to the response to anti-TNF therapy.MethodsFor this objective, a prospective cohort of n = 80 RA patients starting anti-TNF therapy was recruited. Serum determinations at baseline were performed for RF, anti-CCP, anti-CarP and anti-PAD4 antibodies using enzyme-linked immunosorbent assays (ELISA). The clinical response to anti-TNF therapy was determined at week 12 using the change in DAS28 score. Association was performed using multivariate linear regression adjusting for baseline DAS28, sex and age.ResultsThe interaction between pairs of antibodies was tested by the addition of an interaction term. We found two highly significant antibody interactions associated with treatment response: anti-CarP with anti-PAD4 (p = 0.0062), and anti-CCP with RF (p = 0.00068). The latter antibody interaction was replicated in an independent retrospective cohort of RA patients (n = 199, p = 0.04).ConclusionsThe results of this study suggest that antibody interaction effects are important factors in the response to anti-TNF therapy in RA.

Cycling of tumor necrosis factor inhibitors versus switching to different mechanism of action therapy in rheumatoid arthritis patients with inadequate response to tumor necrosis factor inhibitors: a Bayesian network meta-analysis.

Introduction:For patients with rheumatoid arthritis (RA) with an inadequate response to tumor necrosis factor inhibitors (TNFi), main options include cycling onto a different TNFi or switching to a biologic/targeted synthetic disease-modifying antirheumatic drug with a different mechanism of action (MOA). This network meta-analysis (NMA) assessed comparative clinical efficacy of cycling versus switching.Methods:We conducted a literature search in MEDLINE, Embase, and Cochrane Library. Outcomes included proportion of patients with 20%, 50%, or 70% response to American College of Rheumatology criteria (ACR20/ACR50/ACR70 response), Disease Activity Score in 28 joints (DAS28) score below 2.6 or between 2.6 and 3.2, mean change in DAS28 score, mean reduction in and proportion of patients achieving a clinically meaningful reduction (⩾0.22) in Health Assessment Questionnaire score, number of serious adverse events (AEs), and withdrawals for any reason/due to AEs/lack of treatment efficacy. To account for the wide range of study populations and designs, we developed three models to conduct the NMA: fixed-effect, random-effects, and hierarchical Bayesian. PROSPERO ID: CRD42019122993.Results:We identified nine randomized controlled trials and 16 observational studies. The fixed-effect model suggested a 0.99 probability that switch was the better strategy for increasing odds of a clinically meaningful improvement in ACR50 [odds ratio (OR): 1.35 (95% credible interval (CI): 0.96–1.81)]. The fixed-effect model also suggested that switch was associated with lower rates of withdrawal for any reasons [OR: 0.53 (95% CI: 0.40–0.68)]. The random-effects and hierarchical Bayesian models suggested additional uncertainty as they considered more variability than the fixed-effect model.Discussion:Results suggest that switching to a drug with a different MOA is more effective and associated with lower rates of withdrawal than cycling to a different TNFi after failure of first-line TNFi. Further trials that directly compare cycling with switching are warranted to better assess comparative efficacy.Plain language summary Assessment of the effectiveness of different drug treatment strategies in patients with rheumatoid arthritis: an analysis of the published literature Rheumatoid arthritis (RA) is a chronic disease in which inflammation affects joints along with the entire body; this may cause significant pain, joint damage, physical disability, a decreased quality of life, and an increased risk of death.Tumor necrosis factor inhibitors (TNFis) are a common choice as first-line drugs to treat RA. Although they are effective in many patients, therapy with a TNFi is not successful within the first year of treatment in approximately one-third of patients due to either a lack of efficacy or safety issues.When TNFi therapy is unsuccessful, the options are to “cycle” to another TNFi or to “switch” to another drug with a different mechanism of action (MOA). Further studies are needed to help doctors decide the best treatment strategy for their patients when treatment with an initial TNFi fails.This study analyzed 25 published studies in which patients were either “cycled” to another TNFi or “switched” to a drug with a different MOA after unsuccessful treatment with an initial TNFi.The results showed that “switching” to a drug with a different MOA was a better treatment strategy than “cycling” to another TNFi; “switching” increased the chance of clinically meaningful improvement in disease status and lowered the chance of having to stop treatment for any reason.

SAT0103 THE EFFECT OF BODYWEIGHT ON RESPONSE TO INTRAVENOUS OR SUBCUTANEOUS TOCILIZUMAB IN PATIENTS WITH RHEUMATOID ARTHRITIS

Background:Tocilizumab is an IL-6 receptor humanised monoclonal antibody treatment option in rheumatoid arthritis (RA) who have not responded or are intolerant of disease modifying anti-rheumatic drugs (DMARDs) or other biologics. Tocilizumab was available initially as an intravenous (IV) preparation, dosed according to weight, and more recently as a subcutaneous (SC) preparation given at 162mg/weekly irrespective of bodyweight.Obesity is highly prevalent in RA and there has been concern that starting or switching patients to SC tocilizumab could reduce its effectiveness in those patients with a higher body weight when compared to IV tocilizumab.Objectives:To investigate the relationship between bodyweight and DAS28 response at 6 months in tocilizumab naïve RA patients starting IV or SC tocilizumab.Methods:The study population comprised RA subjects recruited to the BSRBR-RA up to 30/11/2018 commencing IV or SC tocilizumab for the first time. Patients had to be tocilizumab naïve and have at least one six monthly study follow-up recorded after starting tocilizumab. Baseline characteristics at point of starting tocilizumab are described. Linear regression, fully adjusted for relevant confounders, was used to investigate the relationship between change in DAS28 score from baseline to six months and body weight per ten kilograms (kg), and in a separate analysis, as BMI category. Multiple imputation was used to handle missing data.Results:1241 patients starting tocilizumab (902 IV, 339 SC) were eligible for analysis. The median age was 59 years, majority were female, and had median disease duration of 11 years at baseline. Over seventy percent had prior biologic exposure. Median weight was 77kg for IV and 76kg for SC starters, and the majority of patients were categorised as normal weight (30% IV, 37% SC) or pre-obesity (31% IV & SC) according to BMI. Median DAS28 score was 5.8 (IV) and 5.5 (SC) at start of treatment with median improvement after 6-months of 1.50 and 2.02 units respectively. The fully adjusted linear regression model showed no association between body weight or BMI and change in DAS28 score at six months for patients starting IV or SC tocilizumab. (Table).TableBaseline VariableIntravenous TCZ patients (n=902)Subcutaneous TCZ patients (n=339)Age, median (IQR)58 (50-67)60 (51-70)Gender, n (%) female708 (78)233 (74)Disease duration, median (IQR) years11 (4-21)11 (4-21)DAS28 score, median (IQR)5.8 (5.1-6.6)5.5 (4.7-6.5)Change in DAS28 score, median (IQR)-1.50 (-3.10 - -0.23)-2.02 (-3.72- -0.37)Weight in KGs, median (IQR)77 (64-91)76 (64-88)Change in DAS28, coefficient (95% CI)Body weight per 10kgs*0.04 (-0.01-0.09)-0.005 (-0.11-0.10)BMI category*Normal weightrefrefUnderweight-0.41 (-1.27-0.46)0.08 (-1.62-1.77)Pre-obesity-0.26 (-0.57-0.05)0.02 (-0.44-0.48)Obesity class I, II & III-0.03 (-0.35-0.29)0.08 (-0.40-0.55)*Fully adjusted for age, gender, disease duration, baseline DAS28 score, baseline HAQ score, co-morbidities, and number of previous biologicsConclusion:Data from this study show that body weight does not appear to affect initial response to IV or SC tocilizumab. This is reassuring given that patients are likely to be given SC tocilizumab due to ease of administration and reduced hospital costs.Disclosure of Interests:Rebecca Davies: None declared, Arani Vivekanantham: None declared, Mark Lunt: None declared, Kath Watson: None declared, Kimme Hyrich Grant/research support from: Pfizer, UCB, BMS, Speakers bureau: Abbvie, James Bluett: None declared

P212 The effect of body weight in response to subcutaneous tocilizumab in patients with RA

Abstract Background Tocilizumab is an IL-6 receptor humanised monoclonal antibody treatment option in rheumatoid arthritis (RA) who have not responded or are intolerant of disease modifying anti-rheumatic drugs (DMARDs) or other biologics. Tocilizumab was available initially as an intravenous preparation, dosed according to weight, and more recently as a subcutaneous (SC) preparation given at 162mg/weekly irrespective of body weight. Obesity is highly prevalent in RA and there has been concern that starting or switching patients to SC tocilizumab could reduce its effectiveness in those patients with a higher body weight. The objective of the current study is to investigate the relationship between body weight and DAS28 response at 6 months in tocilizumab naïve RA patients starting SC tocilizumab. Methods The study population comprised RA subjects recruited to the BSRBR-RA up to 30/11/2018 commencing SC tocilizumab for the first time. Patients had to be tocilizumab naïve and have at least one six monthly study follow-ups recorded after starting tocilizumab. Baseline characteristics at point of starting tocilizumab are described. Linear regression, fully adjusted for relevant confounders, was used to investigate the relationship between change in DAS28 score from baseline to six months and body weight per ten kilograms (kg), and in a separate analysis, as BMI category. Multiple imputation was used to handle missing data. Results Three hundred and fifteen patients starting SC tocilizumab were eligible for analysis. The median age was 60 years, majority were female, and had median disease duration of 11 years at baseline. Seventy percent had prior biologic exposure. Median weight was 76kg, and the majority of patients were categorised as normal weight (37%) or pre-obesity (31%) according to BMI. Median DAS28 score was 5.5 at start of treatment with median improvement after 6-months of 2.0 units. The fully adjusted linear regression model showed no association between body weight or BMI and change in DAS28 score at six months (Table 1). Conclusion Data from this study show that body weight does not appear to affect initial response to SC tocilizumab. This is reassuring given that patients are likely to be given subcutaneous tocilizumab due to ease of administration and reduced hospital costs. Disclosures R. Davies None. A. Vivekanantham None. M. Lunt None. K. Watson None. K.L. Hyrich None. J. Bluett None.

Relationship Between Baseline and Early Changes in C-Reactive Protein and Interleukin-6 Levels and Clinical Response to Tocilizumab in Rheumatoid Arthritis.

ObjectiveTo clarify the relevance of measuring interleukin‐6 (IL‐6) and C‐reactive protein (CRP) levels in order to predict clinical response to tocilizumab (TCZ) in rheumatoid arthritis patients.MethodsIn a pooled, post hoc analysis of 5 pivotal trials of TCZ, we examined the distributions of baseline serum concentrations of IL‐6 and CRP, stratified by randomized treatment group, and week 24 Disease Activity Score in 28 joints (DAS28) status (DAS28 <2.6 versus DAS28 ≥2.6). Relationships between early biomarker changes and later changes in DAS28 scores were evaluated using Spearman's correlations and scatterplots. Finally, percentage changes from baseline in IL‐6 and CRP levels were evaluated.ResultsDistributions of baseline IL‐6 and CRP levels were similar for patients who achieved DAS28 scores <2.6 within 6 months of TCZ initiation and those who did not. Correlations between early changes in these 2 biomarkers and change in DAS28 scores were low (rho < 0.3 for all). Mean percentage increases from baseline in IL‐6 concentrations were observed in all treatment groups (highest in the 8 mg/kg dose group); mean percentage decreases in CRP concentrations were greater at week 2 and at all visits for the 8 mg/kg dose group.ConclusionBaseline serum concentrations of IL‐6 and CRP may not be predictive of clinical outcomes after TCZ treatment. Data demonstrate the efficacy of TCZ in patients across a broad range of baseline serum IL‐6 and CRP concentrations. Similarly, changes in these biomarkers after TCZ dosing are expected and may or may not correspond to changes in other clinical signs and symptoms. These results complement previous reports describing the complex interactions among biomarker changes, other therapeutic mechanisms of action, and clinical outcomes.

A longitudinal genome-wide association study of anti-tumor necrosis factor response among Japanese patients with rheumatoid arthritis.

BackgroundStudies of Caucasian patients with rheumatoid arthritis (RA) to identify genetic biomarkers of anti-tumor necrosis factor (TNF) response have used response at a single time point as the phenotype with which single nucleotide polymorphism (SNP) associations have been tested. The findings have been inconsistent across studies. Among Japanese patients, only a few SNPs have been investigated. We report here the first genome-wide association study (GWAS) to identify genetic biomarkers of anti-TNF response among Japanese RA patients, using response at 2 time-points for a more reliable clinical phenotype over time.MethodsDisease Activity Scores based on 28 joint counts (DAS28) were assessed at baseline (before initial therapy), and after 3 and 6 months in 487 Japanese RA patients starting anti-TNF therapy for the first time or switching to a new anti-TNF agent. A genome-wide panel of SNPs was genotyped and additional SNPs were imputed. Using change in DAS28 scores from baseline at both 3 (ΔDAS-3) and 6 months (ΔDAS-6) as the response phenotype, a longitudinal genome-wide association analysis was conducted using generalized estimating equations (GEE) models, adjusting for baseline DAS28, treatment duration, type of anti-TNF agent and concomitant methotrexate. Cross-sectional analyses were performed using multivariate linear regression models, with response from a single time point (ΔDAS-3 or ΔDAS-6) as phenotype; all other variables were the same as in the GEE models.ResultsIn the GEE models, borderline significant association was observed at 3 chromosomal regions (6q15: rs284515, p = 6.6x10−7; 6q27: rs75908454, p = 6.3x10−7 and 10q25.3: rs1679568, p = 8.1x10−7), extending to numerous SNPs in linkage disequilibrium (LD) across each region. Potential candidate genes in these regions include MAP3K7, BACH2 (6q15), GFRA1 (10q25.3), and WDR27 (6q27). The association at GFRA1 replicates a previous finding from a Caucasian dataset. In the cross-sectional analyses, ΔDAS-6 was significantly associated with the 6q15 locus (rs284511, p = 2.5x10−8). No other significant or borderline significant associations were identified.ConclusionThree genomic regions demonstrated significant or borderline significant associations with anti-TNF response in our dataset of Japanese RA patients, including a locus previously associated among Caucasians. Using repeated measures of response as phenotype enhanced the power to detect these associations.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-016-0920-6) contains supplementary material, which is available to authorized users.

Circulating Th17 cells and joint inflammation during anti-tumour necrosis factor therapy in rheumatoid arthritis

BackgroundAnti-tumour necrosis factor (TNF) agents have revolutionised the treatment of rheumatoid arthritis, although a substantial proportion of patients respond inadequately. Studies in murine and human arthritis have paradoxically shown that anti-TNF treatment can increase circulating interleukin-17-producing T helper (Th17) cells but the association of these changes with treatment responses remains unclear. To investigate immune correlates of anti-TNF treatment response in patients with rheumatoid arthritis we did a longitudinal study using serial clinical, ultrasonographic, and T-cell immunological assessments. Methods25 patients with rheumatoid arthritis naive to biological therapy were followed at four predetermined protocol visits during the first 12 weeks of anti-TNF-alpha treatment. 16 patients were treatment responders, as defined by improvement in disease activity score in 28 joints (DAS28) by more than 1·2 from baseline. Nine patients were non-responders (change in DAS28 score <1·2 from baseline). Changes in synovial thickening and vascularity of metacarpophalangeal joints were quantitatively assessed by power Doppler ultrasonography (PDUS). Changes in the frequency of circulating Th17 cells were evaluated by ELISPOT and intracellular cytokine staining of peripheral blood mononuclar cells. Statistical analysis included Wilcoxon signed rank matched pairs test and Spearman's rank correlation. Written informed consent was obtained from study participants, and ethics approval was obtained from the local ethics committee. This study is registered with ClinicalTrials.gov, number NCT01060098. FindingsELISPOT analysis showed a significant increase in circulating IL17-producing cells 12 weeks after anti-TNF initiation (baseline vs 12 weeks: mean 466 spSFC/106 [SD 277] vs 759 [510]; p=0·003). Fluorescence-activated cell sorting analysis confirmed significant increase in CD4+IL17+ cells at treatment week 12 (baseline vs 12 weeks: mean 0·78% [0·5] vs 1·1 [0·5]; p=0·01). The dynamics of changes in circulating Th17 cells during anti-TNF-alpha treatment were the same in treatment responders and non-responders and in patients treated with different types of anti-TNF alpha agents, suggesting a class effect. The increase in circulating Th17 cells during treatment correlated with reduction in synovial vascularity (r=−0·68, p=0·007) and synovial thickening (r=−0·39; p=0·04) as determined by PDUS. Higher numbers of circulating Th17 cells at baseline were associated with poorer response to anti-TNF-alpha treatment as defined by DAS28 score and ultrasonographic measures. InterpretationThis is the first study, to our knowledge, that links changes in circulating Th17 cells evaluated by cellular assays with resolution of ultrasonographic features of synovitis during anti-TNF treatment. The findings could mean that Th17 cells are redistributed from inflamed joints during treatment or that TNFα could have a role in the regulation of Th17 cell production. FundingThe Kennedy Trust for Rheumatology Research, Imperial College Healthcare Charity, UK Medical Research Council.

Effect of immunogenicity on efficacy of long-term treatment of rheumatoid arthritis with adalimumab

BackgroundAdalimumab is a monoclonal antibody that targets the inflammatory cytokine tumour necrosis factor α and is effective in the treatment of rheumatoid arthritis. However efficacy of treatment with monoclonal antibodies can decrease over time after initial response. One explanation is the development of immunogenicity leading to the development of antibodies against the drug. Radioimmunoassay (RIA) is a sensitive method to detect anti-drug antibodies and has been previously reported to predict long-term efficacy. Our aim was to evaluate the occurrence of antibodies against adalimumab in a cohort of patients with rheumatoid arthritis followed longitudinally from therapy initiation and to test the association with treatment response. MethodsIn a prospective, multicentre study, serum samples from patients with rheumatoid arthritis treated with adalimumab were collected at 3, 6, and 12 months after treatment initiation. Antibodies to adalimumab were measured with RIA at each timepoint, with the disease activity score in 28 joints (DAS28) measured at baseline and each visit (high disease activity >5·1, moderate 3·2–5·1, low <3·2, in remission <2·6). The change in DAS28 scores at 12 months from baseline was defined as the primary outcome. Findings125 adalimumab-treated patients were available with clinical and biological samples at 3, 6, and 12 months for evaluation of immunogenicity. Mean age was 56 years (SD 12, 70% women). At treatment onset with adalimumab, most patients had never previously received a biological drug (112/125 [90%]), with 109 patients (87%) receiving concomitant disease modifying treatment. Mean DAS28 score at baseline was 5·8 (SD 0·3). Anti-adalimumab antibodies were detected in 31 patients (24%) at one or more timepoints after 12 months of treatment. By 12 months, patients who had developed anti-drug antibodies showed less improvement in disease activity than did patients without antibodies (mean change in DAS28=2·35, 95% CI 1·67–3·03 vs 3·15, 2·86–3·35; p=0·022). InterpretationSerum antibodies against adalimumab are associated with poorer response to treatment in rheumatoid arthritis. Anti-drug antibodies were detected using RIA, even though trough serum samples were not always obtained, reflecting a pragmatic clinical approach. Pharmacological monitoring to detect anti-drug antibodies in patients with rheumatoid arthritis on monoclonal antibody biological therapy might be useful in the prediction of long-term treatment response. FundingUK Medical Research Council [grant number G1000417/94909], ICON, GlaxoSmithKline, AstraZeneca, the Medical Evaluation Unit, Arthritis Research UK (grant number 20385).

OP0088 Changes in Baseline Severity of Inflammatory Polyarthritis Over Time

BackgroundPrevious research has suggested that the severity of rheumatoid arthritis (RA) has decreased over time.ObjectivesTo examine the pattern of disease severity in patients with inflammatory polyarthritis (IP) at time of...

AB0521 A single-arm, open-label study of the safety and effectiveness of tocilizumab in combination with methotrexate, in patients with rheumatoid arthritis in latin america – preliminary effectiveness results-ritmo study

ObjectivesTo present the preliminary effectiveness data of TCZ + MTX treatment, with regard to reduction in signs and symptoms over 6 months in Latin American pts with mod/severe RA, MTX-IR.MethodsRitmo...

AB0285 First real life experience with certolizumab pegol in rheumathoid arthritis (ra) in latinamerica

BackgroundCertolizumab pegol (CZP) is a novel TNF inhibitor, consisting of a humanized Fab’ fragment fused to a 40-kd polyethylene glycol moiety with proved efficacy and safety in multiple RA clinical...

OP0231-HPR Predictors of no Improvement in Subjective Health Perception in Newly Diagnosed RA Patients with a Good DAS28 Response at 12 Months in the Dream Tight Control Cohort

BackgroundModern treatment strategies are highly successful in reducing disease activity in rheumatoid arthritis (RA). However, changes in clinical measures of disease activity may not always correspond with a patient’s own...

FRI0243 Act-life study: patterns of tocilizumab use, and dosing among patients with rheumatoid arthritis in the clinical practice.

BackgroundCurrently, there is not substantial evidence about tocilizumab (TCZ) use for the treatment of rheumatoid arthritis (RA) outside of clinical trials.ObjectivesTo describe usage patterns and dosage of TCZ, as well...

AB0946 Anti-TNF treated psoriatic arthritis: Course of composite disease activity measures and clinical core domains

BackgroundPsoriatic arthritis (PsA) is an inflammatory arthritis associated with psoriasis, and The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) has defined clinical core domains for assessment...

THU0174 Impact of IL-6R and IL-6ST Polymorphisms on Response to Anti-TNF Therapy in UK Patients – Results from the Braggss Cohort

BackgroundAnti-tumour necrosis factor (anti-TNF) biologic therapy is a highly effective yet expensive treatment for patients with Rheumatoid Arthritis (RA). Patient eligibility for therapy and response to treatment is assessed using...

Differential effects of decoy receptor‐ and antibody‐mediated tumour necrosis factor blockage on FoxP3 expression in responsive arthritis patients

Our aim was to clarify if anti-tumour necrosis factor (TNF) drugs have effect on expression of three splice forms of FoxP3 mRNA in blood CD4+ T cells from rheumatoid arthritis (RA) patients compared with healthy controls. Forty-five rheumatoid arthritis patients treated with anti-TNF therapy were investigated in a 12-week prospective cohort study. FoxP3 isoforms, CD25 and CTLA-4 mRNA in blood CD4+ T cells were measured with quantitative real-time PCR. Patients benefitting from the treatment, based on changes in DAS28 scores, revealed a significant decrease in expression of full-length FoxP3 following 12 weeks treatment with TNF receptor 2 fusion protein (Etanercept), but not following treatment with anti-TNF antibodies (Adalimumab or Infliximab). A partial normalization of the CTLA-4/FoxP3fl ratio and a correlation between clinical improvement and change in FoxP3 mRNA expression were also seen in Etanercept responders. These changes were not observed in responsive patients treated with the antibody therapies. Our data suggest that TNF decoy receptor and anti-TNF antibodies differ in their effect on FoxP3 expression in responsive patients. As Etanercept binds both TNF-α and Lymphotoxin-α (LT-α), whereas the antibodies only target TNF-α, LT-α may regulate FoxP3 expression in a subset of RA patients. Our findings support the view that anti-TNF treatment is mainly symptomatic.

Association of the response to tumor necrosis factor antagonists with plasma type I interferon activity and interferon‐β/α ratios in rheumatoid arthritis patients: A post hoc analysis of a predominantly Hispanic cohort

AbstractObjectiveDespite the substantial clinical efficacy of tumor necrosis factor α (TNFα) antagonist therapy in patients with rheumatoid arthritis (RA), some patients respond poorly to such agents. Since an interferon (IFN) signature is variably expressed among RA patients, we investigated whether plasma type I IFN activity might predict the response to TNF antagonist therapy.MethodsRA patients (n = 35), the majority of whom were Hispanic, from a single center were evaluated before and after initiation of TNF antagonist therapy. As controls, 12 RA patients from the same center who were not treated with a TNF antagonist were studied. Plasma type I IFN activity was measured using a reporter cell assay, and disease status was assessed using the Disease Activity Score in 28 joints (DAS28). Levels of interleukin‐1 receptor antagonist (IL‐1Ra) were determined in baseline plasma samples using a commercial enzyme‐linked immunosorbent assay. The clinical response was classified according to the European League Against Rheumatism criteria for improvement in RA.ResultsPlasma type I IFN activity at baseline was significantly associated with clinical response (odds ratio 1.36 [95% confidence interval 1.05–1.76], P = 0.020), with high baseline IFN activity associated with a good response. Changes in DAS28 scores were greater among patients with a baseline plasma IFNβ/α ratio &gt;0.8 (indicating elevated plasma IFNβ levels). Consistent with the capacity of IFNβ to induce IL‐1Ra, elevated baseline IL‐1Ra levels were associated with better therapeutic outcomes (odds ratio 1.82 [95% confidence interval 1.1–3.29], P = 0.027).ConclusionThe plasma type I IFN activity, the IFNβ/α ratio, and the IL‐1Ra level were predictive of the therapeutic response in TNF antagonist–treated RA patients, indicating that these parameters might define clinically meaningful subgroups of RA patients with distinct responses to therapeutic agents.

Tolerance and effectiveness of anti–tumor necrosis factor α therapies in elderly patients with rheumatoid arthritis: A population‐based cohort study

Limited data have been published on tolerance to and efficacy of classic or biologic disease-modifying antirheumatic drugs in elderly patients with rheumatoid arthritis (RA). The goal of the present study was to evaluate the tolerance to and effectiveness of anti-tumor necrosis factor (anti-TNF) agents in elderly patients (> or =65 years old) with RA (ERA) in comparison with younger patients (YRA). The Swiss Clinical Quality Management program for RA is a longitudinal population-based cohort. All patients who had received at least 1 dose of anti-TNF agents between January 1997 and November 2005 were included and categorized according to their age. Tolerance was assessed by analyzing discontinuation rates of anti-TNF agents. Effectiveness of these agents was assessed by analyzing RA disease activity (Disease Activity Score in 28 joints [DAS28]) and functional disability (Health Assessment Questionnaire [HAQ]) after anti-TNF initiation. Among 1,571 patients with RA treated with anti-TNF agents, 344 were > or =65 years of age at treatment initiation. Drug discontinuation rates (median time 3 years) and mean change in DAS28 scores at 2 years (-0.65 versus -0.58) were identical in ERA and YRA. However, HAQ score improved significantly less in ERA (-0.02) than in YRA (-0.1) and a subsequent analysis revealed that this finding was essentially due to patients >75 years of age. Age in itself should not interfere with the decision to treat elderly patients with RA with anti-TNF agents. In a subset of patients ages >75 years, no functional improvement according to HAQ should be expected despite improvements in disease activity.